Abstract Layered minerals and materials are ubiquitous and characterized by the frequent occurrence of stacking defects. In particular, interstratification (or mixed layering), which corresponds to the intimate intergrowth of layers differing in terms of their layer thickness and/or internal structure, and stacking faults, both random and well defined, are especially common. These defects impact heavily on the reactivity of the lamellar structures. In addition, they may record the conditions of mineral (trans)formation. Determining their nature, abundance and possibly their distribution is thus an essential step in their structural characterization leading to an understanding of their reactivity. Over recent decades, modelling of X-ray diffraction profiles has proved to be an important tool which allows detailed structural identification of defective lamellar structures. The present chapter will review the basic concepts of such identification and review the literature to outline how our understanding of defective structures and mixed layers has improved over the last decade or so and to describe some of the new perspectives opened by this improvement.